The mechanisms by which proteins are packaged into secretory granules are not understood. Two models that have been proposed are l) self-association or aggregation and 2) recognition of a sorting sequence. These models have not been distinguished experimentally. In GH cells transfected with DNA sequences for human growth hormone, estradiol increases storage of rat prolactin but does not affect storage of human growth hormone. In GH cells transfected with DNA sequences for human prolactin, estradiol does not induce the storage of either rat or human prolactin, although both are still synthesized and secreted. These three molecules are structurally similar. This project will substitute portions of these hormones into each other to determine which amino acids are necessary to allow regulation of storage, and test specific models for packing prolactin into secretory granules.